Thyroid FNAKey Cytology and Histology for Clinicians

Zubair W. Baloch, MD, PhDProfessor of Pathology & Laboratory Medicine

UPENN Medical Center Perelman School of Medicine

Faculty/Presenter Disclosure

Faculty: [Zubair Baloch, MD, PhD]

Relationships with commercial interests: None

Objectives of Thyroid FNA

Recognize specific diagnostic entities

Provide meaningful, management oriented diagnosis

Potential utilization of ancillary techniques

Thyroid FNA Bethesda Classification Scheme

The Bethesda System for Reporting Thyroid Cytopathology:

Implied Risk of Malignancy and Recommended Clinical Management

Diagnostic Category Risk of Malignancy

(%)

Usual Management

Non-diagnostic or Unsatisfactory Repeat FNA with ultrasound

guidance

Benign 0-3% Clinical follow-up

Atypia of Undetermined Significance or

Follicular Lesion of Undetermined

Significance (AUS/FLUS)

~ 5-15% Repeat FNA

Follicular Neoplasm or Suspicious for a

Follicular Neoplasm (Specify if Hurthle

type or Oncocytic)

15-30% Surgical lobectomy

Suspicious for Malignancy 60-75% Near-total thyroidectomy or

surgical lobectomy

Malignant 97-99% Near-total thyroidectomy

Easy-Breezy Thyroid Pathology

Concordant Ultrasound Features, FNA cytomorphology & Histologic

Follow-up

Nodular Goiter

Colloid: Generally abundant . Follicular cells Variable morphologyOncocytes, MacrophagesDegeneration/regeneration: Calcification, stromal proliferation, mitoses

Chronic Lymphocytic Thyroiditis

OncocytesLymphocytes: In the background & infiltrating the cell groups

Papillary Thyroid Carcinoma

Nuclear features Major Diagnostic FeaturesElongation, chromatin clearing, Nuclear membrane irregularities Intranuclear groovesInclusionsSmall peripheral nucleoli

Not so easy - Head Scratching Everyday Thyroid Cytopathology

Intdeterminate Lesions

Or

Indeterminate Pathologist?

Thyroid FNA Bethesda Classification Scheme

The Bethesda System for Reporting Thyroid Cytopathology:

Implied Risk of Malignancy and Recommended Clinical Management

Diagnostic Category Risk of Malignancy

(%)

Usual Management

Non-diagnostic or Unsatisfactory Repeat FNA with ultrasound

guidance

Benign 0-3% Clinical follow-up

Atypia of Undetermined Significance or

Follicular Lesion of Undetermined

Significance (AUS/FLUS)

~ 5-15% Repeat FNA

Follicular Neoplasm or Suspicious for a

Follicular Neoplasm (Specify if Hurthle

type or Oncocytic)

15-30% Surgical lobectomy

Suspicious for Malignancy 60-75% Near-total thyroidectomy or

surgical lobectomy

Malignant 97-99% Near-total thyroidectomy

Diagnosis Follicular Neoplasm

80% Benign on Surgical Excision

DiagnosisFollicular Lesion / Neoplasm

Microfollicles in FNA Specimens

Microfollicles = Neoplasm

Is It That Easy

Dont Think So

Microfollicles

Inter-observer Agreement on Microfollicles Renshaw AA et al. (Arch Pathol Lab Med 2006)

12 cytopathologists were shown 45 small groups of follicular cells 20 Microfollicles

7 Macrofollicles

18 Indeterminate

Microfollicles

Mowschenson PM et al (Surgery 1994)

FNA of normal thyroid tissue may result in the misdiagnosis of micro-follicular lesions

42 cases

9 unremarkable

18 microfollicular

3 mixed macromicrofollicular

1 Hurthle cell

1 Papillary carcinoma

The Atypical Category

The Dreaded AUS/FLUS

Lets Talk About FLUS/AUSResponsible Factors

History TFTs, H/O prior FNA

Ultrasound features Cystic vs. solid

Operator sampling

Adequacy

Cytology Preparation

Interpretation

Surgical follow-up ? Gold standard

The so Called Gold Standard

Case-1

Case 1Thyroid Experts Diagnoses

The Cytopathologists Gold Standard

Diagnoses: Hyperplastic nodule BenignorFollicular Adenoma Benignor Follicular Variant of Papillary Thyroid Carcinoma - Malignant

LiVolsi Rosai Asa Lloyd

Case 1 - Sampling

Benign

Malignant

Case 2 Lesional Morphology

Benign

Atypical Architecture

Case 3History of Prior FNA-

Making Sense of Atypia

Markedly Atypical Cells

Case 4: Inadequate History 52-year-old woman. Ultrasound Left thyroid lobe occupied by a predominantly

ill-defined hypoechoic structure suspicious for anaplastic carcinoma

Original Diagnosis Suspicious for Anaplastic

CarcinomaMore History

Transient symptomatic hyperthyroidism (TSH

0.03) followed by hypothyroidism.

Current medication: Synthroid

Second opinion DxSuspect sub-acute

thyroiditisSurgical excision of

left lobe

Dealing with AUS/FLUSThe Dreaded Call From the Clinician

Too ManyFLUS Cases

What is going on?

HUP Experience

Year % of Total Non-Gyn Cases Cases Diagnosed as AUS/FLUS % of Total Thyroid FNA Biopsied

at HUP

2009 8.5% 96 10.5%

2010 7.84% 88 9%

2011 8.9% 89 8%

HUP ExperienceRates and Interpretations

How to Relay The AUS/FLUS Diagnosis

Explain, Explain & Explain

HUP Experience

AUS/FLUS cases are further sub-classified into Following subcategories (SC):

SC1 - favor benign, however, a follicular neoplasm (FN) could not be excluded due to increased cellularity

SC2 - specimens with focal nuclear overlapping and crowding SC3 - scant specimens with focal nuclear overlapping and crowding SC4 - specimens with focal nuclear overlapping and crowding in a

background of lymphocytic thyroiditis SC5 - few cells with features suspicious for papillary thyroid cancer

(PTC) SC6 - specimens in which a FN cannot be excluded (with

miscellaneous morphologic descriptors).

0.00% 5.00% 10.00% 15.00% 20.00% 25.00% 30.00% 35.00% 40.00%

SC1

SC2

SC3

SC4

SC5

SC6

Malignancy Rate by AUS-FLUS Subtype

What I have Learned so Far

Thyroid FNA diagnoses vary among pathologist

History and Sampling is as important as the Interpretation

AUS/FLUS is a useful category

Rates

Follow-up

Ancillary testing

Modern ApproachA Gentle Mix of Old and New

Nothing is 100%

My View

History Clinical features; TFTs Ultrasound Characteristics Cytologic Interpretation (have you talked to your

pathologist) Ancillary Studies

Which pass(es) are being selected for molecular studies Selected cases Test selection Test results vs. cytologic interpretation

Histologic follow-up

Abu-al Qasim (936-1013 AD)Kitab al-Tasrif

He described thyroid nodules/enlargements as this tumor, which is called Elephant of the throat, is a large tumor which commonly occurs in women and is of congenital and acquired types. The congenital type is incurable, whereas, the acquired type is of two types: one resembles sebaceous cyst and other as an arterial aneurysm which is dangerous to incise, so never apply knife to it unless the tumor is small.